Toruniak, Poland

Safety and Efficacy of Upadacitinib in Combination With Topical Corticosteroids in Children From 2 to Less Than 12 Years of Age in Japan With Moderate to Severe Atopic Dermatitis

Japanese Coronary Intervention Using Drug Eluting and Perfusion Therapy for Left Main Disease (JDEPTH-LM Registry)

JDEPTH-LM Registry is a prospective observational multi-center study. The investigators will enroll and treat patients in the registry who meet the selection criteria under usual care and for whom PCI with W-KBT following on crossover stenting for LMT-LAD direction, proximal optimization technique (POT), and conventional kissing balloon technique (C-KBT) is the optimal treatment. The operators shall obtain oral or written consent from patients who meet the criteria before performing PCI, indicating the intention to perform PCI with W-KBT, and shall keep records. The investigators will continuously register cases attempting PCI with W-KBT according to the protocol and evaluate its efficacy and safety using data from this multi-center registry.

CT-Angiography Plaque Characteristics and Events in Deferral Patients by Invasive Fractional Flow Reserve

Although fractional flow reserve (FFR)-guided percutaneous-coronary-intervention (PCI) has improved short- and middle-term outcome compared with angiography-guided PCI alone, cardiac-events still occur in FFR-deferral patients in long-term.1-4 Recent J-CONFIRM registry examined 1263 patients with 1447 lesions in whom revascularization was deferred based on FFR in the 28 centers.5 While 2-year target vessel failure (TVF) rate was 5.5% in deferred lesions in the J-CONFIRM registry, 5-year TVF raised up 11.6% in deferred lesions.5, 6 The TVF rate raised up from 5.5% to 11.6% in the last 3 years mainly due to clinically driven target-vessel-revascularization (TVR) in the registry.5, 6 In the DEFER trial, patients with FFR > 0.75 were randomly assigned to PCI deferral (Defer) or performance (Perform) and patients showing FFR < 0.75 underwent PCI (Reference).3 The 5-year cardiac death and acute myocardial infarction (AMI) rate were excellent in the Defer group as compared to Perform and Reference groups (3.3%, 7.9%, and 15.7%, p < 0.003, respectively).4 However, 15-year follow-up of the DEFER study revealed that all cause of mortality and TVR were similar among Defer, Perform and Reference groups (mortality; 33.0% vs. 31.1% vs. 36.1% p= 0.441 respectively, and TVR; 36.3% vs. 27.8% vs. 35.4%, p= 0.522 respectively).7 Favorable initial 5-year clinical outcome in deferral patients has been lost during 15-year follow-up in the DEFER study. It is urgent issue to disclose the factor to predict future cardiac events in deferral lesions. The failure of PCI to modify long-term outcomes may stem from its inability to modify the underlying atherosclerotic process. Furthermore, recent PREVENT study disclosed that in patients with non-flow-limiting (FFR >0.80) vulnerable coronary plaques identified by intracoronary imaging, preventive PCI reduced major adverse cardiac events (MACE) arising from high-risk vulnerable plaques, compared with optimal medical therapy (OMT) alone8. Although their high-risk vulnerable plaques were defined using intracoronary imaging but not coronary CT angiography (CTA) in the PREVENT study, the presence of high-risk vulnerable plaque without flow-limiting (FFR >0.80) frequently caused the subsequent cardiac events in patients without the initial PCI. While CTA is known to be useful to evaluate coronary artery plaque features as well as stenosis severity, high-risk plaque (HRP) on coronary CTA defined as a combination of positive remodeling (PR) and low attenuation plaque (LAP) has been reported to be associated with the future cardiac events.9-12 Gallone and coworkers reported in their meta-analysis that high-risk coronary plaque characteristics significantly predicted patient-level and lesion-level major adverse cardiac event (MACE) in the future, using various high-risk coronary plaque definitions by several intracoronary imaging modalities and CTA.13 The investigators hypothesized that CTA could identify plaque features linked to future cardiac events in deferral patients. To determine the predictive factors for future cardiac events in FFR-based deferral patients, the investigators examined clinical features and plaque characteristics on CTA in the deferral lesions based on invasive FFR in consecutive 373 patients with chronic coronary syndromes (CCS).

Glycogen Storage Disease Type Ia (GSDIa) Disease Monitoring Program

The DTX401-CL401 Disease Monitoring Program (DMP) is a prospective, multicenter, long-term observational study to follow up participants with GSDIa for at least 10 years after the administration of DTX401.

Avacopan vs Reduced-dose Glucocorticoids in ANCA-associated Vasculitis

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis is characterized by a small to medium-size vasculitis and the presence of ANCA. ANCA-associated vasculitis includes microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. ANCA-associated vasculitis can be a life-threatening disease and the mortality is 80% at 1 year in untreated patients. In 2010s, standard therapies for remission induction of ANCA-associated vasculitis were the combination of high-dose glucocorticoids and either cyclophosphamide or rituximab. Although those therapies have high remission rates of 80-90%, mortality at 5 years is still high at 10-20% mainly due to treatments-related adverse events. In the LoVAS trial (2021, JAMA), the combination of reduced-dose glucocorticoid and rituximab showed non-inferiority to high-dose glucocorticoid and rituximab in remission rates at 6 months. In addition, adverse events were dramatically less in the reduced-dose group than in the high-dose group. In the ADVOCATE trial (2021, NEJM), the combination of avacopan, newly developed complement C5a inhibitor, and rituximab or cyclophosphamide showed non-inferiority to high-dose glucocorticoid and rituximab or cyclophosphamide in remission rates at 6 months. The avacopan group was allowed to use glucocorticoid within 1 month from the trial entry, and over 80% of patients used glucocorticoid indeed. Regarding adverse events, they were less in the avacopan group than in the glucocorticoid group. Although both the reduced-dose glucocorticoid regimen in the LoVAS trial and the avacopan regimen in the ADVOCATE trial are effective and safe for patients with ANCA-associated vasculitis, there is no trial directly comparing both regimens at the moment. Thus, in this multicenter, open-label, randomized, non-ineriority, phase 4 trial, the investigators aim to investigate if the combination of avacoapn, short-term (4 weeks) reduced-dose glucocorticoid and rituximab is non-inferior to the combination of reduced-dose glucocorticoid (20 weeks) and rituximab. The investigators also compare safety profiles and disease relapse between the two groups. A total of 160 patients with new-onset ANCA-associated vasculitis (microscopic polyangiitis and granulomatosis with polyangiitis) will be recruited and randomized to the two treatments groups. The primary end point is remission rate at 26 weeks, and the patients will be followed until 104 weeks for assessing disease relapse and long-term safety.

Zephyr Valve Japan Post-Marketing Surveillance

This is a multicenter, prospective, observational surveillance across 20 centers in Japan enrolling 140 consecutive adult patients with hyperinflation of the lungs due to severe emphysema who are considered to be appropriate candidates for BLVR using Zephyr Endobronchial Valve (EBV, Pulmonx Corporation) and confirmed to have little to no collateral ventilation in the target lobe. Enrolled (consented) subjects will undergo a bronchoscopy procedure with the Chartis assessment to confirm that little to no collateral ventilation is present (CV- status) followed by EBV placement in the most diseased lobe. Subject will be hospitalized for a minimum of 3 nights for observation and followed up for 12 months. Subjects with collateral ventilation will be exited from the surveillance without treatment. The primary endpoint is incidence rate of pneumothorax at Day 45 post-index procedure. The effectiveness will be evaluated from Baseline to specified timepoint based on changes in lung function, exercise capacity, dyspnea and quality of life. A high-resolution computed tomography (HRCT) will be performed at Day 45 and Month 12 to determine Treated Lobe Volume Reduction (TLVR). Lung function will be assessed at Month 3, 6 and 12 by measuring post-bronchodilator forced expiratory volume in 1 second (FEV1), residual volume (RV) and 6 Minutes Walking Distance. The safety will be evaluated based on incident rate of treatment emergent adverse events through Month 12. Subjects will be required to complete a pulmonary rehabilitation program between Day 45 and Month 3 per local/national guidelines.

A Study of TAK-279 in Adult Participants With Generalized Pustular Psoriasis or Erythrodermic Psoriasis

Clinical Study of Rituximab for the Treatment for Idiopathic Membranous Nephropathy with Nephrotic Syndrome

A Study to Evaluate Effectiveness and Safety of Deucravacitinib (BMS-986165) Compared With Placebo in Participants With Active Systemic Lupus Erythematosus

Study to Assess Change in Disease Activity and Adverse Events of RINVOQ in Adult Participants With Ankylosing Spondylitis in the Real-World Japan